A brief review on bitter apple - Pharmacological activities

Present review article reveals the importance of Bitter Apple belonging to the species Citrullus colocynthis, distributed in India and other parts of the world; this extensive research information on this species is highly significant for future researchers worldwide. As per Ayurveda and Siddha system of medicine it is Tikta-rasam, ushna-veeryam and katuvipakam and used as purgative, diuretic, lagu, kapharam and abortifacient. Fruit is bitter, pungent and used as purgative, anthelmintic, antipyretic, carminative, cures tumors, leucoderma, ulcers, asthma, etc. Root is useful in jaundice, ascites, urinary disease, rheumatism. In this article pharmacological and biological activity, inputs have been extensively recorded and discussed.

Review Article https://doi.org/10.20546/ijcmas.2018.712.034

A Brief Review on Bitter Apple - Pharmacological Activities

Rashmi Sagar* and V.K Dumka

Department of Veterinary Pharmacology and Toxicology, Guru Angad Dev Veterinary and

Animal Sciences University, Ludhiana-141001, Punjab, India

*Corresponding author

A B S T R A C T

Introduction

Bitter Apple also known as Citrullus

colocynthis (L.) Schrad (Cucurbitaceae) has

medicinal and ornamental purposes, the

former derived primarily from the fruit pulp

(de Smet, 1997)

Common names for this plant include

colocynth, bitter gourd, bitter apple, and bitter

cucumber in English while it is known as

Koloquinthe in German and coloquintein

French (de Smet, 1997) C colocynthis has

only one accepted name but six synonyms

(The Plant List, 2017)

In India and Pakistan, it is known as tumba

(Mahajan and Kumawat, 2013; Hussain et al.,

2014)

Importance and Uses

According to Hussain et al., (2014), C

colocynthis has the following traditional

medicinal uses: “diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wound, mastitis, and in gastrointestinal disorders such as indigestion, constipation, dysentery, gastroenteritis, colic pain and different microbial infections.” Also, according to the same authors, who wrote a comprehensive review on several properties of C colocynthis, indicated that there are multiple

medicinal and biological activities, including antidiabetic, anticancer, cytotoxic, antioxidant, antilipidemic, insecticidal, antimicrobial and anti-inflammatory De Smet (1997) also reviewed earlier literature on the

International Journal of Current Microbiology and Applied Sciences

ISSN: 2319-7706 Volume 7 Number 12 (2018)

Journal homepage: http://www.ijcmas.com

Present review article reveals the importance of Bitter Apple belonging to the species

Citrullus colocynthis, distributed in India and other parts of the world; this extensive

research information on this species is highly significant for future researchers worldwide

As per Ayurveda and Siddha system of medicine it is Tikta-rasam, ushna-veeryam and katuvipakam and used as purgative, diuretic, lagu, kapharam and abortifacient Fruit is bitter, pungent and used as purgative, anthelmintic, antipyretic, carminative, cures tumors, leucoderma, ulcers, asthma, etc Root is useful in jaundice, ascites, urinary disease, rheumatism In this article pharmacological and biological activity, inputs have been extensively recorded and discussed

K e y w o r d s

Bitter apple, Citrullus

colocynthis (L.) Schrad

(Cucurbitaceae)

Accepted:

04 November 2018

Available Online:

10 December 2018

Article Info

medicinal properties of C colocynthis

Several accessions have shown resistance to

several viruses and diseases (Dabauza et al.,

1997) Dabauza et al., (1997) developed an

Agrobacterium tumefaciens-mediated genetic

transformation protocol in which 7-day-old

seedling cotyledons were infected with strain

LBA4404 carrying the binary vector pBI121,

harboring the β-glucuronidase (gus; reporter)

and the neomycin phosphotransferase (nptII;

marker) genes Based on GUS expression,

14% of explants were shown to be

transformed PCR confirmed the integration

of the gusand nptIIgenes while Southern blot

analysis conferred transmission of the

gusgene to several transgenic plants obtained

by selfing C colocynthis is able to withstand

extreme desert temperatures through a high

rate of transpiration to lower leaf

temperatures below lethal temperatures

(Althawadi and Grace, 1986)

Anti-inflammatory and analgesic activity

Marzouk et al., 2011 studied aqueous extracts

of C colocynthis fruit and seed at an

immature stage for anti-inflammatory activity

using the carrageenan-induced paw edema

assay in rats

The best anti-inflammatory activities were

obtained with immature fruits from south

Tunisia Therefore, C colocynthis could be a

useful product suitable for further evaluation

for inflammatory diseases

Methanol extract of Citrullus colocynthis

significantly inhibited carrageenan, serotonin

and prostaglandin E1-induced paw edema

Maximum inhibition was observed in

prostaglandin E1-induced paw edema In

carrageenan air-pouch model, methanol

extract of Citrullus colocynthis significantly

reduced the volume of exudate and migration

of neutrophils and monocytes The extract

significantly decreased formation of

granuloma tissue in chronic inflammation model Hence, this investigation established some pharmacological evidences to support

the use of Citrullus colocynthis as anti-inflammatory agent (Rajamanickam et al.,

2010)

Anticandidal and antibacterial activity

Bactericidal activities of crude extracts, fractions and compounds of Citrullus colocynthis plant aerial parts and ripe

deseeded fruits were performed against the drug sensitive standard strain of

Mycobacterium tuberculosis H37Rv (ATCC

27294), 16 drug resistant strains of

Mycobacterium tuberculosis and two Mycobacterium other than tuberculosis (MOTT) strains, using radiometric BACTEC system Methanolic extract of ripe deseeded

fruit of Citrullus colocynthis showed good

activity (MIC ≤ 62.5 μg/ml) and one of the bioactive fractions demonstrated the best

Mycobacterium tuberculosis H37Rv (Mehta

et al., 2013)

The maximum antimicrobial activity was exhibited by acetone, ethanol, methanol and

distilled water extract of the fruits of Citrullus

colocynthis against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Shigella shigellae and Candida albicans

Whereas petroleum ether extract was found to

be less effective against test strains (Rodge and Biradar 2013)

In the study conducted by Sagar et al., 2018

various extractsviz alcoholic, acetone,

chloroform of the leaves of Citrullus

colocynthis were evaluated for antibacterial

activity against Staphylococcus aureus and

E.coli and it was observed that none of the

extracts showed antibacterial activity against both the bacteria when compared to standard antibiotic

Antioxidant potential

The antioxidant effects of Citrullus

colocynthis seeds extracts [a crude aqueous

extract (E1), a defatted aqueous extract (E2),

a hydromethanolic extract (HM), an ethyl

acetate extract (EA) and a n-butanol extract

(n-B)] were studied at a concentration of 2

000 μg/ml in a 1,1-diphenyl-2-picrylhydrazyl

assay, reducing percentage of 88.8% with EA,

74.5% with HM and 66.2% with E1 was

recorded with a corresponding IC50 of 350,

580 and 500 μg/ml respectively as compared

to 1.1 μg/ml for ascorbic acid (Benariba et al.,

2013)

Antioxidant activity of Citrullus colocynthis

seed methanolic extract was studied

spectrophotometrically by 1,

1-diphenyl-2-picryl hydrazyl and hydrogen peroxide free

radical scavenging method The methanolic

seed extract of Citrullus colocynthis showed

maximum percentage inhibition of 79.4 and

72.4% by 1, 1-diphenyl-2-picryl hydrazyl and

hydrogen peroxide method respectively at 300

μg /ml (Gill et al., 2011)

In vitro antioxidant studies revealed that,

maximum percentage inhibition of DPPH

radicals by methanolic extract of Citrullus

colocynthis fruits (MECC) was 62% at 800

μg/ml In the nitric oxide radical scavenging

model, the maximum percentage inhibition by

MECC was about 56% at 800μg/ml From the

study, it was concluded that MECC

demonstrated dose dependent antioxidant

activity comparable with ascorbic acid

(Jayaraman and Christina 2013)

Hypoglycemic activity

Agarwal et al., 2012 examined the effect of

root of C colocynthis on the biochemical

parameters of normal and alloxan-induced

diabetic rats Diabetes mellitus was induced

by intraperitoneal (120 mg/kg b.wt.) injection

of alloxan monohydrate for three days and the animals showing blood glucose level in the range of 175-300 mg/dL were selected for study The blood glucose concentrations of the animals were measured at the beginning

of the study and the measurements were repeated on 3rd, 5th and 7th day after the start

of the experiment Aqueous extract of roots of

Citrullus colocynthis showed significant

reduction in blood sugar level (58.70%) when compared with chloroform (34.72%) and ethanol extracts (36.60%) The aqueous extracts showed improvement in parameters like body weight, serum creatinine, serum urea and serum protein as well as lipid profile and also restored the serum level of bilirubin total, conjugated bilirubin, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP)

The direct in vitro effects of Citrullus

colocynthis seed extracts were evaluated in

glucose-stimulated insulin release from pancreatic islets isolated from rats Six extracts were tested, a crude aqueous, defatted aqueous, ethyl acetate, H2O-methanol, n-butanol extract and an extract containing a mixture of the major component (fraction A) (identified by gel chromatography in the ethyl acetate), n-butanol and H2O-methanol extracts The majority of extracts exhibited a positive insulinotropic action when tested in the presence of 8.3 mM D-glucose (Benariba

et al., 2013)

The effect of Citrullus colocynthis pulp

extract on the structure of the liver was tested

in diabetic rats at both light and scanning electron microscopic levels Diabetes caused degenerative alterations in the form of disorganization of the hepatic cords, cytoplasmic vacuolization and pyknosis of the nuclei of hepatocytes and inflammatory cell infiltration Scanning electron microscope examination of these livers revealed

numerous lipid droplets within hepatocytes,

damaged blood sinusoids and hemorrhage of

erythrocytes between hepatocytes and inside

Disse’s spaces The liver of Citrullus

colocynthis -treated rats revealed minor

histological changes versus the control

animals (Khalil et al., 2010)

Anti – alopecia activity

Dhanotia et al., 2011 evaluated C colocynthis

for hair growth activity in androgen-induced

alopecia Petroleum ether extract of C

colocynthis was applied topically for its hair

growth-promoting activity Alopecia was

induced in albino mice by testosterone

administration intramuscularly for 21 days Its

inhibition by simultaneous administration of

extract was evaluated using follicular density,

anagen/telogen (A/T) ratio and microscopic

observation of skin sections Finasteride

(5α-reductase inhibitor) solution was applied

topically and served as positive control

Petroleum ether extract of C colocynthis

exhibited promising hair growth promoting

activity, as reflected from follicular density,

A/T ratio and skin sections The treatment

was also successful in bringing a greater

number of hair follicles in anagenic phase

than the standard finasteride The result of

treatment with 2 and 5% petroleum ether

extracts were comparable to the positive

control finasteride The petroleum ether

extract of C colocynthis and its isolate was

found useful in the treatment of

androgen-induced alopecia

Petroleum ether and ethanol extracts of

Citrullus colocynthis were tested for their

effect on hair growth in albino rats The

extracts incorporated into oleaginous

ointment base were applied topically on

shaved denuded skin of albino rats The time

required for initiation of hair growth as well

as completion of hair growth cycle was

recorded Minoxidil 2% solution was applied

topically and served as the standard Hair growth initiation time was significantly reduced to half on treatment with the petroleum ether extracts compared with untreated control animals The time required for complete hair growth was also considerably reduced The treatment was successful in bringing a greater number of hair follicles (>70%) to anagenic phase than standard minoxidil (67%) The result of treatment with 2 and 5% petroleum ether extracts were comparable with the standard

minoxidil (Roy et al., 2007)

Antiparasitic insecticidal and antiscorpion effects

Albino mice were intraperitionally infected

with promastigotes of Leishmania donovani

inoculation of albino mice caused elevation of liver and spleen weight after 7-15 days The mice treated with 20-100 mg/kg from

Citrullus colocynthis showed decreased average liver and spleen weight in comparison to the positive control The most important histopathologcal results in the positive control including scattered necrosis, lymphatic infiltration, proliferation of macrophages and a variable number of leishman bodies were observed and it was

noted that 80-100 mg/kg of Citrullus

colocynthis returned liver section to normal

histology (Al-Harmni et al., 2012)

Methylene chloride, n-hexane, chloroform

and ethanol extracts of Citrullus colocynthis fruits were tested against Aphis craccivora

The highest insecticidal effect (LC50: 11003 ppm) was obtained from the ethanol extract The residue remaining after evaporation of ethanol extract was re-extracted by different solvents with increasing polarity Each

fraction was tested against Aphis craccivora

The butanol extract showed the maximum insecticidal effect The effective compound

was identified as

2-O-β-D-glucopyranosylcucurbitac in E (Torkey et al.,

2009)

Citrullus colocynthis was evaluated as new

envenomation mainly Androctonus australis

hector venom (Aah) Local action (paw

edema) and systemic effects (inflammatory,

metabolic parameters, oxidative stress and

hyperglycemia) were studied in pretreated

mice with Citrullus colocynthis (50 mg/kg);

30 min before injection of sublethal dose of

Androctonus australis hector venom (10

μg/20 g) Results showed that injected

Citrullus colocynthis extract before

envenomation was able to protect animals

against the toxicity of the venom It

significantly reduced paw edema, cell

migration, exudation and hyperglycemia

Citrullus colocynthis decreased also some

inflammatory markers (MPO and EPO

activities, CRP and C3) and maintain the level

of CPK, ASAT and ALAT So, it was

concluded that Citrullus colocynthis appeared

to be a potential tool that can reduce

pathophysiological effects induced after

envenomation (inflammation and oxidative

stress) (Fatima and Mohamed 2014)

Growth inhibitory activity on breast cancer

cells

Grossman et al., 2007 studied the effects of

cucurbitacin glycosides extracted from

Citrullus colocynthis leaves on human breast

cancer cell growth Leaves were extracted,

resulting in the identification of cucurbitacin

B/E glycosides The cucurbitacin glycoside

combination (1:1) inhibited growth of ER (+)

MCF-7 and ER (-) MDA-MB-231 human

breast cancer cell lines Cell-cycle analysis

showed that treatment with isolated

cucurbitacin glycoside combination resulted

in accumulation of cells at the G (2)/M phase

of the cell cycle Treated cells showed rapid

reduction in the level of the key protein complex necessary to the regulation of G (2) exit and initiation of mitosis, namely the p34 (CDC2)/cyclin B1complex Cucurbitacin glycoside treatment also caused changes in the overall cell morphology from an elongated form to a round-shaped cell, which indicates that cucurbitacin-treatment caused impairment of actin filament organization This profound morphological change was thought to influence intracellular signaling by molecules such as PKB, resulting in inhibition

in the transmission of survival signals Reduction in PKB phosphorylation and inhibition of survivin, an anti-apoptosis family member, was observed The treatment caused elevation in p-STAT3 and in p21 (WAF), proven to be a STAT3 positive target

in absence of survival signals Cucurbitacin glycoside treatment also induced apoptosis, as measured by Annexin V/propidium iodide staining and by changes in mitochondrial membrane potential (DeltaPsi) using a fluorescent dye, JC-1 It was suggested that cucurbitacin glycosides exhibit pleiotropic effects on cells causing both cell cycle arrest and apoptosis These results indicated that

therapeutic value against breast cancer cells

The paper reviewed Citrullus colocynthis as

promising medicinal plant with wide range of pharmacological activities which could be utilized in several medical applications because of its effectiveness and safety

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How to cite this article:

Rashmi Sagar and Dumka, V.K 2018 A Brief Review on Bitter Apple - Pharmacological

Activities Int.J.Curr.Microbiol.App.Sci 7(12): 281-287

doi: https://doi.org/10.20546/ijcmas.2018.712.034